CCL2/CCR2-Dependent Recruitment of Th17 Cells but Not Tc17 Cells to the Lung in a Murine Asthma Model

被引:44
作者
Wang, Aili
Wang, Zhengyun
Cao, Yong
Cheng, Sheng
Chen, Huilong
Bunjhoo, Hansvin
Xie, Jungang
Wang, Congyi
Xu, Yongjian
Xiong, Weining [1 ,2 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Resp & Crit Care Med, Wuhan 430030, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Minist Hlth, Key Lab Pulm Dis, Wuhan 430030, Peoples R China
基金
中国国家自然科学基金;
关键词
Asthma; CC chemokine ligand 2; Tc17; cells; Th17; Airway inflammation; MONOCYTE CHEMOTACTIC PROTEIN-1; BRONCHOALVEOLAR LAVAGE FLUID; AIRWAY INFLAMMATION; CC CHEMOKINES; MOUSE MODEL; ALLERGIC INFLAMMATION; ACUTE EXACERBATION; ENDOTHELIAL-CELLS; MIP-1; ALPHA; MICE;
D O I
10.1159/000371764
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Interleukin (IL)-17 has been implicated in the pathogenesis of asthma and the progression of airway inflammation. Here, we used a model of allergic asthma and found that the frequencies of IL-17-secreting T helper (Th) 17 and CD8 (Tc) 17 cells were both significantly increased, as was the expression of the CC chemokine receptor (CCR2) on the surface of these cells. CC chemokine ligand 2 (CCL2) has been shown to mediate the activation and recruitment of inflammatory cells in asthma, which are also skewed after ovalbumin (OVA) challenge. However, the role of CCL2 on Th17 cells and Tc17 cells in asthma has not been illuminated. Methods: Mice that were sensitized and challenged with OVA received anti-CCL2 antibody (Ab; 5 mu g/day intratracheally) or CCR2 antagonist (RS504393, 2 mg/kg/day intraperitoneally) prior to the challenge. Some mice received an iso-type control Ab or vehicle alone. We then assessed the effects of allergic asthma and anti-CCL2 Ab or CCR2 antagonist treatment on the levels of IL-17 and CCL2, the Th17 and Tc17 cell frequencies and lung tissue inflammation. Results: We demonstrated that CCL2 and IL-17 levels and the frequency of Th17 and Tc17 cells in lung tissues and bronchoalveolar lavage fluid increased in the asthma group compared with the normal control mice. Blocking the CCL2/CCR2 axis greatly reduced the Th17 but not the Tc17 cell frequency, and revealed a suppressive effect on airway inflammation. Conclusion: These findings indicate a role for the CCL2/CCR2 axis in mediating Th17 but not Tc17 cell migration during acute allergic airway inflammation. (C) 2015 S. Karger AG, Basel
引用
收藏
页码:52 / 62
页数:11
相关论文
共 42 条
[1]   Increased MCP-1, RANTES, and MIP-1 alpha in bronchoalveolar lavage fluid of allergic asthmatic patients [J].
Alam, R ;
York, J ;
Boyars, M ;
Stafford, S ;
Grant, JA ;
Lee, J ;
Forsythe, P ;
Sim, T ;
Ida, N .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1996, 153 (04) :1398-1404
[2]  
Campbell EM, 1999, J IMMUNOL, V163, P2160
[3]   Sequential Evaluation of Serum Monocyte Chemotactic Protein 1 Among Asymptomatic State and Acute Exacerbation and Remission of Asthma in Children [J].
Chan, Chin-Kan ;
Kuo, Ming-Ling ;
Yeh, Kuo-Wei ;
Ou, Liang-Shiou ;
Chen, Li-Chen ;
Yao, Tsung-Chieh ;
Huang, Jing-Long .
JOURNAL OF ASTHMA, 2009, 46 (03) :225-228
[4]   A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case-control and a family study in Tunisia [J].
Chelbi, H. ;
Ghadiri, A. ;
Lachheb, J. ;
Ghandil, P. ;
Hamzaoui, K. ;
Hamzaoui, A. ;
Combadiere, C. .
GENES AND IMMUNITY, 2008, 9 (07) :575-581
[5]   The Role of the CCL2/CCR2 Axis in Mouse Mast Cell Migration In Vitro and In Vivo [J].
Collington, Sarah J. ;
Hallgren, Jenny ;
Pease, James E. ;
Jones, Tatiana G. ;
Rollins, Barrett J. ;
Westwick, John ;
Austen, K. Frank ;
Williams, Timothy J. ;
Gurish, Michael F. ;
Weller, Charlotte L. .
JOURNAL OF IMMUNOLOGY, 2010, 184 (11) :6114-6123
[6]   Innate IL-17-producing cells: the sentinels of the immune system [J].
Cua, Daniel J. ;
Tato, Cristina M. .
NATURE REVIEWS IMMUNOLOGY, 2010, 10 (07) :479-489
[7]   The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness [J].
Gonzalo, JA ;
LLoyd, CM ;
Wen, DY ;
Albar, JP ;
Wells, TNC ;
Proudfoot, A ;
Martinez, C ;
Dorf, M ;
Bjerke, T ;
Coyle, AJ ;
Gutierrez-Ramos, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (01) :157-167
[8]   Release of RANTES, MIP-1 alpha, and MCP-1 into asthmatic airways following endobronchial allergen challenge [J].
Holgate, ST ;
Bodey, KS ;
Janezic, A ;
Frew, AJ ;
Kaplan, AP ;
Teran, LM .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1997, 156 (05) :1377-1383
[9]  
JahnzRozyk KM, 1997, J INVEST ALLERG CLIN, V7, P254
[10]   Serum Eosinophil Cationic Protein and 27 Cytokines/Chemokines in Acute Exacerbation of Childhood Asthma [J].
Kato, Masahiko ;
Yamada, Yoshiyuki ;
Maruyama, Kenichi ;
Hayashi, Yasuhide .
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 2010, 152 :62-66